6V02

N-terminal 5 domains of CI-MPR

Summary for 6V02

• Entry DOI: 10.2210/pdb6v02/pdb
• Related: 6P8I
• Descriptor: Cation-independent mannose-6-phosphate receptor, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: lectin, receptor, protein transport, sugar binding protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 81421.01

Authors

Olson, L.J.,Dahms, N.M.,Kim, J.-J.P. (deposition date: 2019-11-18, release date: 2020-09-30, Last modification date: 2024-10-16)

Primary citation

Olson, L.J.,Misra, S.K.,Ishihara, M.,Battaile, K.P.,Grant, O.C.,Sood, A.,Woods, R.J.,Kim, J.P.,Tiemeyer, M.,Ren, G.,Sharp, J.S.,Dahms, N.M.
Allosteric regulation of lysosomal enzyme recognition by the cation-independent mannose 6-phosphate receptor.
Commun Biol, 3:498-498, 2020

PubMed Abstract: The cation-independent mannose 6-phosphate receptor (CI-MPR, IGF2 receptor or CD222), is a multifunctional glycoprotein required for normal development. Through the receptor's ability to bind unrelated extracellular and intracellular ligands, it participates in numerous functions including protein trafficking, lysosomal biogenesis, and regulation of cell growth. Clinically, endogenous CI-MPR delivers infused recombinant enzymes to lysosomes in the treatment of lysosomal storage diseases. Although four of the 15 domains comprising CI-MPR's extracellular region bind phosphorylated glycans on lysosomal enzymes, knowledge of how CI-MPR interacts with ~60 different lysosomal enzymes is limited. Here, we show by electron microscopy and hydroxyl radical protein footprinting that the N-terminal region of CI-MPR undergoes dynamic conformational changes as a consequence of ligand binding and different pH conditions. These data, coupled with X-ray crystallography, surface plasmon resonance and molecular modeling, allow us to propose a model explaining how high-affinity carbohydrate binding is achieved through allosteric domain cooperativity.

PubMed: 32908216
DOI: 10.1038/s42003-020-01211-w

Experimental method

X-RAY DIFFRACTION (2.46 Å)